3D In Vitro Models of Breast Cancer: Current Challenges and Future Prospects Toward Recapitulating the Microenvironment and Mimicking Key Processes

Abstract Each year, ≈1.6 million women are diagnosed with breast cancer worldwide. Of these cases, 0.5 million result in death, with over 90% of these deaths resulting from metastasis. Since it is one of the top 5 cancers with the highest mortality rates, the development of breast cancer models that are physiologically relevant to the human body is severely needed. This includes models of the breast tissue microenvironment, the microenvironment of metastatic sites (e.g., brain, lungs, bone, liver), and models specifically mimicking each individual step of the cancer metastatic cascade. This review focuses on models of the primary tumor environment for studying cell invasion and spread within the mammary tissue, prior to metastatic outgrowth. Using a combination of methods such as tumor spheroids, 3D printed biomaterials, and microfluidic designs, a variety of 3D in vitro modeling methods exist to recapitulate specific aspects of the tumor microenvironment and understand sources of tumor heterogeneity. An effective model can be specified for each patient, eliminating the need for human trials. Subsequently, as the mechanisms involved in breast cancer metastasis are studied utilizing more effective in vitro models, targeted therapeutics can be discovered, thus advancing clinical treatment strategies.